The term “ G-protein ”, without specification, usually refers to membrane-bound heterotrimeric G-proteins , sometimes also called large G-proteins (as opposed to smaller, monomeric so-called small GTPases ). These heterotrimeric G proteins are activated upon binding of the ligand agonist to the G-linked metabotropic receptor . They are composed of three subunits called alpha (G α ), beta (G β ) and gamma (G γ ). [1] The last two βγ subunits dissociate together upon binding of the ligand to the receptor and functionally make up a doublet, therefore they are called the “beta-gamma complex” (“βγ-complex”) or “beta-gamma-dimer" ("βγ-dimer") .
| Heterotrimer G-protein | |
|---|---|
| Identifiers | |
| Cipher cf | 3.6.5.1 |
| CAS Number | 9059-32-9 |
| Enzyme bases | |
| Intenz | Intenz view |
| BRENDA | BRENDA entry |
| Expasy | NiceZyme view |
| Metacyc | metabolic pathway |
| Kegg | KEGG entry |
| PRIAM | profile |
| PDB structures | RCSB PDB PDBe PDBj PDBsum |
| Gene ontology | AmiGO • EGO |
| Search | |
| PMC | articles |
| PubMed | articles |
| NCBI | NCBI proteins |
| Cas | 9059-32-9 |
There are four main families of G-proteins: G i / G o , G q , G s , and G 12 . [2]
Content
Alpha Subunit
The subunit G α consists of two domains: GTPase and α-helical . Experiments conducted in the 1980s showed that delineated subunits of G α can directly activate effector enzymes. The GTP-bound form of the α-subunit of the transducine protein (G t ) activates the cGMP-phosphodiesterase of the optic cells of the rods [3] , and the GTP-bound form of the α-subunit of the stimulating protein G (G s ) activates the hormone-sensitive adenylate cyclase [4] [5] .
There are at least 20 different types of G α subunits distributed over four different protein families based on the homology of their primary sequences: [6]
| G protein family | α subunit | Gene | Signal cascade | G-protein-associated metabotropic receptors (examples) | Effects (examples) |
|---|---|---|---|---|---|
| Inhibitory Family G i | |||||
| G i / o | G αi , G αo | GNAO1, GNAI1, GNAI2, GNAI3 | Inhibition of adenylate cyclase activity, opening of potassium channels , closing of calcium channels | Muscarinic cholinergic receptors of types M 2 and M 4 , [7] chemokine receptors, α 2 -adrenoreceptors , serotonin receptors of subtype 5-HT1 , histamine receptors of subtype H 3 and H 4 , dopamine receptors of subtype D 2 and the like | Smooth muscle contraction , decreased neuronal activity |
| The family of "visual" G t | G αt (Transducin) | GNAT1, GNAT2 | Phosphodiesterase 6 activation | Rhodopsin | Visual signal transmission |
| Taste- Sensitive Family G gust | G αgust (Gustducin) | GNAT3 | Phosphodiesterase 6 activation | Taste buds | Flavor Transmission |
| G z | G αz | Gnaz | Inhibition of adenylate cyclase activity | ? | Maintaining the ionic balance of perilymphatic and endolymphatic cochlear fluids. |
| Stimulating Family G s | |||||
| Stimulating Family G s | G αs | GNAS | Adenylate cyclase activation | β-adrenergic receptors ; Serotonin receptors of subtypes 5-HT 4 , 5-HT 6 and 5-HT 7 ; Dopamine D 1 -like receptors, histamine H 2 receptors | Increased heart rate , relaxation of smooth muscles , stimulation of neuronal activity. |
| The olfactory family G olf | G αolf | GNAL | Adenylate cyclase activation | olfactory receptors | Olfactory signal transmission |
| Family G q | |||||
| Family G q | G αq , G α11 , G α14 , G α15 , G α16 | GNAQ, GNA11, GNA14, GNA15 | Phospholipase C activation | α 1 -adrenoreceptors , muscarinic cholinergic receptors of subtypes M 1 , M 3 and M 5 , [7] histamine receptors of subtype H 1 , serotonin receptors of subtype 5-HT 2 | Smooth muscle contraction, calcium ion current |
| Family G 12/13 | |||||
| Family G 12/13 | G α12 , G α13 | GNA12, GNA13 | Activation of the Rho family of GTPases | Cell cytoskeletal changes, smooth muscle contraction | |
Beta Gamma Dimer
The beta and gamma subunits of the G protein are closely related to each other, and they are called the beta gamma complex . After activation of the G-protein-coupled G receptor, the βγ- dimer dissociates from the bond with the Gα-subunit after the Gα-subunit hydrolyzes GTP to HDF .
Function
The free G βγ dimer can work as an effector molecule by itself, it can activate other secondary mediator systems, or it can open and close ion channels .
For example, a G βγ dimer bound to histamine H 1 receptors, after dissociation, can activate phospholipase A2, which leads to the formation of arachidonic acid . At the same time, the G βγ dimer bound to muscarinic cholinergic receptors can directly open G-linked potassium channels of internal rectification , and the G βγ dimer bound to histamine H 3 receptors can open L-type calcium channels .
Notes
- ↑ Hurowitz EH, Melnyk JM, Chen YJ, Kouros-Mehr H., Simon MI, Shizuya H ;. Genomic characterization of the human heterotrimeric G protein alpha, beta, and gamma subunit genes (English) // DNA Research : journal. - 2000. - Vol. 7 , no. 2 . - P. 111-120 . - DOI : 10.1093 / dnares / 7.2.111 . - PMID 10819326 .
- ↑ Ellis, Claire. The state of GPCR research in 2004 // Nature Reviews Drug Discovery : journal. - 2004 .-- July ( vol. 3 , no. 7 ). - P. 577-626 . - DOI : 10.1038 / nrd1458 .
- ↑ Fung, BKK; Hurley, JB; Stryer, L. Flow of information in the light-triggered cyclic nucleotide cascade of vision // Proceedings of the National Academy of Sciences of the United States of America : journal. - 1981. - Vol. 78 , no. 1 . - P. 152-156 . - DOI : 10.1073 / pnas . 78.1.152 . - PMID 6264430 .
- ↑ Cerione, RA; Sibley, DR; Codina, J; Benovic, JL; Winslow, J; Neer, EJ; Birnbaumer, L; Caron, MG; Lefkowitz, RJ; and others et al. Reconstitution of a hormone-sensitive adenylate cyclase system. The pure beta-adrenergic receptor and guanine nucleotide regulatory protein confer hormone responsiveness on the resolved catalytic unit (English) // Journal of Biological Chemistry : journal. - 1984. - Vol. 259 , no. 16 . - P. 9979-9982 . - PMID 6088509 .
- ↑ May, DC; Ross, EM; Gilman, AG; Smigel, MD Reconstitution of catecholamine-stimulated adenylate cyclase activity using three purified proteins (Eng.) // Journal of Biological Chemistry : journal. - 1985. - Vol. 260 , no. 29 . - P. 15829-15833 . - PMID 2999139 .
- ↑ Strathmann MP, Simon MI; Simon G alpha 12 and G alpha 13 subunits define a fourth class of G protein alpha subunits // Proceedings of the National Academy of Sciences of the United States of America : journal. - 1991. - Vol. 88 , no. 13 . - P. 5582–5586 . - DOI : 10.1073 / pnas.88.13.5582 . - PMID 1905812 .
- ↑ 1 2 Kou Qin, Chunmin Dong, Guangyu Wu & Nevin A Lambert; Dong; Wu; Lambert. Inactive-state preassembly of Gq-coupled receptors and Gq heterotrimers (Eng.) // Nature Chemical Biology : journal. - 2011 .-- August ( vol. 7 , no. 11 ). - P. 740-747 . - DOI : 10.1038 / nchembio.642 . - PMID 21873996 .